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Alkylating Agent; Vinca Alkaloid

Selumetinib vs Carboplatin/Vincristine for Brain Cancer

Phase 3

Recruiting

Led By Jason R Fangusaro

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that has not been treated with any modality other than surgery

Patients must have the ability to swallow whole capsules

Must not have

Treatments and/or medications patient is receiving that would make her/him ineligible, such as Supplementation with vitamin E greater than 100% of the daily recommended dose, Surgery within 2 weeks prior to enrollment

Ophthalmologic conditions: Current or past history of central serous retinopathy, Current or past history of retinal vein occlusion or retinal detachment, Patients with uncontrolled glaucoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed up to 3 years after accrual completion

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing if selumetinib works as well or better than the standard treatment (carboplatin/vincristine) for patients with low-grade glioma associated with NF1.

Who is the study for?

This trial is for children and young adults aged 2 to 21 with Neurofibromatosis type 1 (NF1) and low-grade glioma (LGG), including tumors of the optic pathway. They must have measurable tumors, no prior tumor-directed therapy except surgery, stable blood pressure, adequate organ function, and not be pregnant or breastfeeding. Participants need to agree to use effective contraception during the study.

What is being tested?

The trial compares Selumetinib—a drug that blocks enzymes needed by tumor cells—with standard chemotherapy drugs Carboplatin/Vincristine in treating NF1-associated LGG. It aims to determine if Selumetinib is as effective or better than standard treatment in improving vision for those with optic pathway tumors.

What are the potential side effects?

Selumetinib may cause heart issues, high blood pressure, skin rash, fatigue, nausea and vomiting. Chemotherapy with Carboplatin/Vincristine can lead to hair loss, nerve damage causing numbness or tingling in hands/feet, hearing problems and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have an untreated NF-1 associated low-grade glioma, except for surgery.

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I can swallow whole capsules.

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I have been diagnosed with neurofibromatosis type 1.

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I can take care of myself but may not be able to do heavy physical work.

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My kidney function is normal or near normal.

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My bilirubin levels are within the normal range for my age.

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I have a newly-diagnosed low-grade glioma with symptoms or findings related to the tumor.

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My blood pressure is 130/80 mmHg or lower.

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My body surface area is at least 0.5 square meters.

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I can understand and speak English or Spanish for assessments.

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I am between 2 and 21 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had surgery in the last 2 weeks and don't take high doses of vitamin E.

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I have no history of serious eye conditions and my glaucoma is under control.

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I am not pregnant.

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I have a heart condition that could increase my risk for heart disease or have had serious heart issues.

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I haven't been treated for another cancer besides surgery in the past year.

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I have not had any treatments like chemotherapy, radiation, immunotherapy, or bone marrow transplant for my cancer.

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I do not have any infections that are not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis, assessed up to 3 years after accrual completion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis, assessed up to 3 years after accrual completion

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization until death from any cause or till the time of last follow-up for patients who are alive at the time of analysis, assessed up to 3 years after accrual completion for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event-free survival (EFS)

Number of participants with visual acuity (VA) improvement per arm

Secondary study objectives

Change in VA using HOTV letter acuity testing

Change in executive function

Change in motor function

+4 more

Other study objectives

Change in circumpapillary retinal nerve fiber layer (cpRNFL) thickness by treatment arm

Change in macular ganglion cell - inner plexiform layer (GCIPL) thickness by treatment arm

GCIPL thickness at baseline by visual acuity (VA) treatment response

+13 more

Side effects data

From 2020 Phase 2 trial • 8 Patients • NCT03040986

100%

Aspartate aminotransferase increased

83%

Edema limbs

83%

Hypoalbuminemia

67%

Fatigue

67%

Hypertension

50%

Abdominal pain

50%

Anemia

50%

Dyspnea

50%

Alkaline phosphatase increased

50%

Anorexia

50%

Alanine aminotransferase increased

50%

Nausea

33%

Dizziness

33%

Hypocalcemia

33%

Generalized muscle weakness

33%

Hyponatremia

33%

Lymphocyte count decreased

33%

Rash maculo-papular

33%

Hypokalemia

33%

Bloating

33%

CPK increased

33%

Cough

33%

Creatinine increased

33%

Vomiting

17%

Heart failure

17%

Pancreatitis

17%

Diarrhea

17%

Dry mouth

17%

Colonic obstruction

17%

Confusion

17%

Gallbladder obstruction

17%

Gallbladder infection

17%

Lipase increased

17%

Serum amylase increased

17%

Ascites

17%

Dysgeusia

17%

Alopecia

17%

Edema trunk

17%

White blood cell decreased

17%

Atelectasis

17%

Dysphagia

17%

Glucose intolerance

17%

Hyperglycemia

17%

Weight loss

17%

Hypomagnesemia

17%

Hypotension

17%

Malaise

17%

Neck pain

17%

Pleural effusion

17%

Postnasal drip

17%

Renal and urinary disorders - Other, Dysuria

17%

Rash acneiform

17%

Neutrophil count decreased

17%

Paresthesia

17%

Peritoneal infection

17%

Back pain

17%

Biliary tract infection

17%

Blood bilirubin increased

17%

Fever

17%

Sore throat

17%

Urinary tract obstruction

17%

Musculoskeletal and connective tissue disorder - Other, muscle spasm

17%

Urine discoloration

100%

80%

60%

40%

20%

Study treatment Arm

Dose Level 0: 75mg Selumetinib Sulfate Twice Daily

75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (selumetinib sulfate)Experimental Treatment4 Interventions

Patients receive selumetinib sulfate PO BID on days 1-28. Treatment is continuous and repeats every 28 days for 27 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.

Group II: Arm I (carboplatin, vincristine)Active Control5 Interventions

INDUCTION: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, 22, 43, 50, 57, and 64 and vincristine IV or IV push over 1 minute on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI during screening and on study. MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study and during follow-up.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Selumetinib Sulfate

2017

Completed Phase 2

~80